In this article we will discuss about the meaning and components of innate immunity.
Meaning of Innate Immunity:
Protection against infection that relies on mechanisms which are existing before the infection, are referred to as innate immunity. It is also called natural or native immunity. This type of immunity is non-specific, i.e., not specific to a particular pathogen, similar kind of immune responses are produced against any pathogen.
This immunity may not distinguish fine differences between foreign substances. It has no memory, i.e., react in essentially the same way to repeated infections. This immunity provides the first line of defence during the critical period just after the hosts’ exposure to pathogen.
Components of Innate Immunity:
The principal components of innate immunity are:
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(1) Physical and chemical barriers, such as epithelia and antimicrobial substances produced at epithelial surfaces.
(2) Phagocytic cells (neutrophils, macrophages) and NK (natural killer) cells.
(3) Blood proteins, including members of the complement system and other mediators of inflammation.
(4) Proteins called cytokines that regulate and coordinate many of the activities of the cells of innate immunity. These components provide four types of defensive barriers. Physical, physiological, phagocytic and inflammatory barriers.
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A. Physical barriers:
Physical or anatomical barriers are provided by the skin, the surface of mucous membranes and cilia.
i. The intact skin not only provides a mechanical barrier that prevents the entry of most pathogens but its low pH also inhibits the growth of most bacteria. The dermis of skin contains blood vessels, hair follicles, sebaceous and sweat glands.
The sebaceous secretions contain unsaturated fatty acids (oleic acid) and free saturated fatty acids that maintain the pH of the skin between 3 and 5. This pH inhibits the growth of many microorganisms. The relatively dry skin with high salt concentration in drying sweat is relatively inhibitory or lethal to many bacteria and fungi.
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ii. The mucous lining of nose, nasopharynx and respiratory tract may trap bacteria and other particulate pathogens from inspired air. The microorganisms that pass through inhaled air beyond the larynx are trapped in the bronchial mucosa and only a few may reach the bronchioles and alveoli.
The hair-like cilia sweep the secretion containing the foreign particulate materials toward the oropharynx, where it is swallowed or coughed out.
The cough reflex plays an important defensive role of respiratory tract. Small particular materials that manage to reach the alveoli may be ingested by phagocytic cells present there. The nasal and respiratory secretions contain mucopolysaccharides which can neutralize influenza and some other viruses.
iii. The synchronous movement of cilia of epithelial mucosal lining of gastrointestinal tract may entrap microorganisms that have entered through food. Furthermore, nonpathogenic microorganisms tend to colonies the intestinal mucosa. These anaerobic normal micro-flora generally outcompete pathogens for attachment sites on the mucosa and prevent super-infection by coliforms during antibiotic therapy.
iv. The conjunctiva is freed of bacteria and dust particles by flushing action of tears (lacrymal secretion).
B. Physiological barrier:
Body temperature, pH and various soluble factors provide chemical or physiological barriers to many pathogens.
i. The low pH of gastric juice acts as a barrier to most of the ingested microorganisms. Newborns are susceptible to some disease that do not afflict adults because their stomach contents are less acidic than those of adults.
ii. Body temperature of certain species may inhibit the growth of many pathogens. For example, Chickens have innate immunity to anthrax because of their high body temperature which inhibits the growth of the virus.
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iii. Lysozyme, a hydrolytic enzyme found in tears and some mucosal secretion is able to cleave peptidoglycan layer of bacterial cell wall.
iv. Interferons, a kind of cytokine produced by virus-infected cells have the ability to bind nearby cells and induce a generalized antiviral state.
v. A number of specific and nonspecific immunologic mechanisms can convert the inactive forms of complement proteins into an active state that enables them to damage the membranes of many non-specific pathogens.
vi. Certain plasma proteins, collectively known as acute phase proteins increase in concentration during acute inflammatory response as a result of infection or tissue injury. These proteins are thought to play defensive role.
vii. Many other substances like beta-lysin, basic polypeptides, properdin etc. are believed to have some antibacterial as well as antiviral effects.
C. Phagocytic barriers:
Once the infective agents have crossed the physical barriers, the tissue factors come into play for body defence through phagocytic activities. Phagocytosis is the ingestion of particulate material, which may include whole pathogenic microorganisms.
Phagocytosis is performed mainly by two types of cells:
(1) Microphages, e.g., polymorphonuclear leucocyte i.e. neutrophils.
(2) Macrophages, e.g., mononuclear phagocytic cells (monocyte and tissue macrophages).
Phagocytic activities can be divided into four stages:
(a) Chemo taxis:
Phagocytes are attracted and move toward a variety of substances generated in an immune response and thus these cells reach the site of infection or toward the pathogens. This process is called chemo taxis.
(b) Attachment (adherence):
The next step of phagocytosis is the attachment or adherence of the antigen to the phagocytic cell membrane. Complex antigens, such as whole bacterial cells or viral particles, tend to adhere well and are readily phagocytosed.
Isolated proteins and encapsulated bacteria tend to adhere poorly and are less readily phagocytosed. Adherence induces the cell membrane to form protrusions called pseudopodia that extend around the attached materials.
(c) Formation of phagosome:
Pseudopodia around the adhered substance then enclose the latter and fuse to form a vacuole called phagosome.
(d) Digestion:
The phagosome then moves toward the cell interior, where it fuses with lysosome to form phagolysosome. Lysosome contains hydrolytic enzymes and many other bactericidal substances, which digest the ingested materials.
(e) Exocytosis:
The digested contents of the phagolysosome are then eliminated in a process called exocytosis.
The antigens to be phagocytosed may be coated with appropriate antibody or complement component. These antigens bind more readily to phagocytic cell membrane. As a result, phagocytosis is enhanced.
Molecules that bind to antigen and phagocytes and enhance phagocytosis are called opsonin (e.g., mannose binding lectin). Most phagocytic cells possess special receptors in their membrane, which following binding with extracellular molecules help in internalisation of those substances.
D. Inflammatory barriers:
Inflammatory response is a localised tissue response to injury or other trauma characterised by pain, heat, redness and swelling. This response includes both localised and systemic effects, consists of altered patterns of blood flow, an influx of phagocytic and other immune cells, removal of foreign antigens and healing of the damaged tissues.
Three major events of inflammatory responses are:
(a) At the site of infection, blood vessels become dilated as the vessels that carry blood away from the affected area become constricted. It results in engorgement of the capillary network causing redness and rise in temperature of the affected area.
(b) Increased capillary permeability facilitates an influx of fluid and cells from the engorged capillaries into the tissue. Such accumulated fluid (exudate) has a much higher protein than the fluid normally released from vasculature. Accumulation of such fluid causes swelling (edema) of the affected area.
(c) Due to increased capillary permeability phagocytes from the capillaries enter the infected tissue site. These cells then phagocytose the bacteria or other invading microorganisms, release lytic enzymes, which can damage nearby healthy cells. Such accumulated dead cells, digested materials of phagocytes and fluid together form a substance called pus.
The whole event of inflammatory response is mediated by several factors. Some of such are released from invading microorganisms, some are released from damaged cells in response to tissue injury, some are generated by serum complement system and some are produced by various white blood cells participating in inflammatory response. Some of such factors are cytokines, C-reactive protein, histamine, kinin, fibrin etc.
Cytokines especially TNF, IL-1 and chemokines activate leucocyte and recruit them at the site of injury. Cytokines also stimulate the expression of adhesion molecules on endothelial cells and thus initiate the recruitment of leucocytes to the sites of infection.
Macrophages that are recruited to the site of infection are activated by microbial products and by NK cell-derived cytokine, IFN-y to phagocytose and kill the microbes.
C-reactive protein is produced by liver cells in response to tissue damage that bind to the C-polysaccharide cell wall component found on a variety of bacteria and fungi. Such binding activates the complement system, resulting in increased clearance of the pathogen.
Histamine, released from mast cell granules binds to receptors on nearby capillaries and venules, causing vasodilation and increased permeability. Tissue injury occurred during inflammation may activate the inactive protein kinins which also cause vasodilation and increased capillary permeability.
A kinin, called bradykinin, can stimulate pain receptors in the skin that in turn protect the injured area. At the site of tissue injury, many enzymes of blood clotting system are stimulated that cause deposition of insoluble strands of fibrin, the main component of blood clot. These fibrin strands wall off the injured area from the rest of the body part and thus prevent spread of infection.
Inflammation thus produces a variety of systemic changes in the host that enhance the ability of the innate immune system to eradicate infection and in severe infection, can contribute to systemic tissue injury or death.